Conoscenza della Food Protein-Induced Enterocolitis Syndrome (FPIES) tra i pediatri di famiglia Pasquale Comberiati Clinica Pediatrica Università di Verona

A multicentre retrospective study of 66 Italian children with FPIES: different management for different phenotypes Sopo MS, CEA 2012; 42:1257 No. of FPIES diagnosis at the 3 centers 18 – 16 – 14 – 12 – 10 – 8 – 6 – 4 – 2 – 0000 2004 2005 2006 2007 2009 2008 2010 17 P < 0.001 15 13 6 4 Retrospective study (2004-2010): Rome, Florence, Benevento 66 children, 165 episodes 35 (53%) OFC diagnosed vs 31 (47%) clinically diagnosed Tolerance OFC 1-year after last reaction

The prevalence and natural course of FPIES to cow’s milk: A large-scale, prospective population based study. Katz Y, JACI 2011; 127:647 Incidence of CM-FPIES vs IgE-CMA Cohort of 13,019 infant (2004-2006) 44 with CM-FPIES and 66 with IgE-CMA 28 (64%) OFC vs 16 (36%) clinically diagnosed CM-FPIES Incidence 0.6 – 0.4 – 0.2 – % 0.34% 0.5% FPIES (n= 44) IgE-CMA (n= 66)

FPIES: The diagnosis is often delayed Lack of suspition No specific diagnostic tests Non-specific presenting symptoms Fiocchi A, Curr Opin Allergy Clin Immunol 2014, 14:246–254

F P I E S Differential diagnosis of food protein-induced enterocolitis syndrome (FPIES) Fiocchi A, Curr Opin All Clin Immunol 2014; 14:246 F P I E S ANAPHYLAXIS SEPSIS GASTROENTERITIS METABOLIC DISORDES PRIMARY IMMUNODEFICIENCY SURGICAL ABDOMINAL CONDITION

Food Protein-Induced Enterocolitis Syndrome (FPIES): 16-Year Experience Mehr S, Pediatrics 2009; 123:e459 1 Episodes 40 – 30 – 20 – 10 – Episodes of Acute FPIES before diagnosis % 29% 20% 26% 2 Episodes 3 Episodes 4 Episodes Retrospective study (1992-2007) 35 patients, with 66 acute FPIES Causative foods, clinical features, treatments, and outcomes

Food Protein-Induced Enterocolitis Syndrome (FPIES): 16-Year Experience Mehr S, Pediatrics 2009; 123:e459 Abdominal Imaging 40 – 30 – 20 – 10 – Additional investigations of FPIES episodes % 34% 2% 22% 28% Septic evaluation Surgical consultat Laparotomy Retrospective study (1992-2007) 35 patients, with 66 acute FPIES Causative foods, clinical features, treatments, and outcomes

OBIETTIVI E METODI Indagine conoscitiva «FPIES» Questionario «on-line» anonimo Google-drive platform 16 domande risposta multipla 194 Pediatri di famiglia Verona (70%) e Torino (30%) Torino Clinica Pediatrica Università di Verona

RISULTATI 12% 49% 31% 8% Conosco sintomi, diagnosi e terapia 0 10 20 30 40 50 12% 31% 49% 8% Conosco sintomi, diagnosi e terapia Mai sentito parlare Sentito solo parlare Non ho familiarità % Clinica Pediatrica Università di Verona

RISULTATI – Alimenti trigger 0 10 20 30 40 50 Altri cibi solidi Latte Vaccino Latte di Soia Pesce 34 5 20% ha in cura b.ni con FPIES 14 Riso 6 24 (Uovo, Cereali, Pollo, Tacchino, Frutta o Verdura) Clinica Pediatrica Università di Verona

Prevalence of trigger foods in FPIES Cow’s Milk 67% 44% 20% 67% Fish 1 % 10% 3% 12% Oats 16% 16% 6% - Soy 41% 41% 34% 4% Poultry 10% 5% 3% 3% Banana 3.5% - 3% - Ruffner (n. 462) Mehr (n. 35) Sopo (n. 66) Egg 11% 3% - 6% Rice 19% 22% 40% 4% Caubet (n. 160) Caubet JC, JACI 2014; 134: 382-9 Ruffner MA. JACI:In Practice 2013; 1: 343-9 Mehr S. Pediatrics 2009; 123:e459. Sopo MS. CEA 2012;42:1257-65.

RISULTATI – Chi ha fatto Diagnosi 0 10 20 30 40 50 49% 5% 8% 38% Allergologo Me Medesimo Pediatra Ospedale/ Pronto Soccorso Gastroenterologo % Clinica Pediatrica Università di Verona

RISULTATI – Casi FPIES 54% 13% 47% 23% FPIES ACUTA FPIES CRONICA 5 mesi, 2 episodi di vomito profuso, pallore e disidratazione comparsi dopo alcune h assunzione crema di riso. FPIES CRONICA 2 mesi, LF dalla nascita, scarsa crescita ponderale, diarrea cronica con muco ± sangue nelle feci, ± leucocitosi. FPIES CRONICA 3 mesi, LF dalla nascita, scarsa crescita ponderale, diarrea cronica con muco ± sangue nelle feci, persistenza sintomi anche dopo inizio eHCF. 54% 47% 23% 13% Clinica Pediatrica Università di Verona

RISULTATI – Test Diagnostici 1 DIAGNOSI FPIES : Prick Test e/o sIgE devono essere negativi? Among 160 subjects with FPIES, 24% had positive specific IgE to the FPIES food, which is referred to as ‘‘atypical’’ FPIES 70 – 60 – 50 – 40 – 30 – 20 – 10 – 00 56% 44% SI NO Caubet JC, JACI 2014; 134: 382-9 Clinica Pediatrica Università di Verona

RISULTATI – Test Diagnostici 2 DIAGNOSI FPIES: sempre FPIES: Diagnosis DIAGNOSI FPIES: sempre necessario il TPO? There are no in vivo or in vitro tests with demonstrated specificity and sensitivity to diagnose FPIES OFC may not be necessary to make the diagnosis if the history of FPIES is very compelling (2 or more reactions with typical symptoms to the same food in a 6-month period and elimination of symptoms when the causative food is removed from the diet) 70 – 60 – 50 – 40 – 30 – 20 – 10 – 00 57% 43% SI NO Boyce J, J Allergy Clin Immunol 2010;126:S1-S58 Clinica Pediatrica Università di Verona

FPIES: Acute Managment TERAPIA FPIES «ACUTA» : Adrenalina cardine? RISULTATI – Terapia 1 FPIES: Acute Managment TERAPIA FPIES «ACUTA» : Adrenalina cardine? Oral rehydration fluids (if mild) Intravenous fluids, 20 ml/kg boluses of isotonic saline (if moderate to severe) Metilprednisolone ev, 1mg/kg (max 60-80mg) (if moderate to severe) Epinephrin for hypotension for severe or unresponsive to fluids 70 – 60 – 50 – 40 – 30 – 20 – 10 – 00 26% 74% SI NO Järvinen KM, JACI in Pract; 2013; 1:317-22 Clinica Pediatrica Università di Verona

Cumulative probability of recovery from CMP-induced FPIES Natural history of food protein-induced enterocolitis syndrome (FPIES) Katz Y, Curr Opin All Clin Immunol 2014; 14:229 Cumulative probability of recovery from CMP-induced FPIES Around 90% of FPIES patients recover by the age 3–5 years. Recovery from FPIES to solid foods occurs later than FPIES to Cow’s Milk or Soy.

FPIES: Long term Managment RISULTATI – Terapia 2 FPIES: Long term Managment A quanti mesi dall’ultima FPIES «acuta» consiglieresti la Reintroduzione dell’alimento? 6-11 mesi 12-18 18-24 Allergologo 60% 70 – 60 – 50 – 40 – 30 – 20 – 10 – 00 17% 15% 8% Around 90% of FPIES patients recover by the age 3–5 years. Oral Food Challenge is warranted to determine when FPIES has resolved 1st Tolerance-OFC with cow’s milk at 18-20 months of age. For other foods reports are insufficient, and should be considered for reintroduction to the diet 12–18 months after the last reaction, in a physician-supervised setting Clinica Pediatrica Università di Verona Järvinen KM, JACI in Pract; 2013; 1:317-22

CONCLUSIONE È necessaria una maggiore informazione riguardo all’FPIES, in merito alle diverse forme cliniche ed alla gestione terapeutica acuta ed a lungo termine. Clinica Pediatrica Università di Verona